The present invention relates to a matrix for sustained-release preparation and a sustained-release preparation comprising it.
EP-A 481732 (Japanese Patent Unexamined Publication No. 112468/1993) describes a base for sustained-release preparation comprising a mixture of polylactic acid and a glycolic acid/hydroxycarboxylic acid [HOCH(C.sub.2-8 alkyl)COOH] copolymer.
Japanese Patent Unexamined Publication No. 212436/1990 describes a base for sustained-release preparation obtained by direct dehydrative poly-condensation process of lactic acid and/or glycolic acid and an oxycarboxylic acid.
Japanese Patent Unexamined Publication No. 173746/1992 describes a sustained-release drug-polymer complex prepared by adding a drug to a polymer mixture of a lactic acid/glycolic acid copolymer and poly-.gamma.-butyrolactone, poly-.delta.-valerolactone and/or poly-.epsilon.-caprolactone.
Japanese Patent Unexamined Publication No. 212423/1987 describes polymers or copolymers of esters of hydroxypoly carboxylic acids such as an ethyl ester of polymalic acid.
Japanese Patent Unexamined Publication No. 92641/1988 describes .beta.-benzylmalate.lactic acid copolymer.
However, these are different in structure from the ester formed at a terminal carboxyl group of a straight-chain polyester which essentially consists of an .alpha.-hydroxymonocarboxylic acid.
In sustained-release preparations wherein a drug is dispersed in a biodegradable polymer, it is desirable that drug release be controlled freely. In general, drug release duration for a sustained-release preparation depends on the composition and molecular weight of the base biodegradable polymer. Initial drug release following administration of the sustained-release preparation is sometimes excessive, which can result in a rapidly increased local drug concentration, and hence a rapidly increased blood level, leading to undesirable action. There is therefore need to develop a matrix for sustained-release preparation enabling production of a sustained-release preparation of low initial drug release.
According to the present invention, there is provided:
(1) A matrix for sustained-release preparation comprising an ester formed at a terminal carboxyl group of a straight-chain polyester which essentially consists of an .alpha.-hydroxymonocarboxylic acid, the polyester having a weight-average molecular weight of about 1,500 to about 50,000, PA0 (2) The matrix according to term (1) above, wherein the straight-chain polyester if a lactic acid/glycolic acid copolymer, PA0 (3) The matrix according to term (1) above, wherein the ester is an alkyl ester, PA0 (4) The matrix according to term (3) above, wherein the alkyl ester is a C.sub.1-3 alkyl ester, PA0 (5) A sustained-release preparation which comprises the matrix as defined in term (1) above and a biologically active peptide, PA0 (6) The sustained-release preparation according to term (5) above, wherein the biologically active peptide is an LH-RH analogue, PA0 (7) The sustained-release preparation according to term (6) above, wherein the LH-RH analogue is an LH-RH antagonist, PA0 (8) The sustained-release preparation according to term (5) above, wherein the biologically active peptide is a cytokine, PA0 (9) The sustained-release preparation according to term (8) above, wherein the cytokine is an interferon, PA0 (10) An injectable preparation which comprises the sustained-release preparation as defined in term (5) above, PA0 (11) An ester formed at a terminal carboxyl group of a straight-chain polyester which essentially consists of an .alpha.-hydroxymonocarboxylic acid, the polyester having a weight-average molecular weight of about 1,500 to about 50,000 PA0 (12) The ester according to term (11) above, which is an ester formed at a terminal carboxyl group of a lactic acid/glycolic acid copolymer, PA0 (13) The ester according to term (11) above, which is an alkyl ester, and PA0 (14) The ester according to term (13) above, which is a C.sub.1-3 alkyl ester.